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Circulating 25-Hydroxyvitamin D Levels Predict Survival in Early-Stage Non–Small-Cell Lung Cancer Patients

Wei Zhou, Rebecca S. Heist, Geoffrey Liu, Kofi Asomaning, Donna S. Neuberg, Bruce W. Hollis, John C. Wain, Thomas J. Lynch, Edward Giovannucci, Li Su, David C. Christiani

From the Departments of Environmental Health, Biostatistics, Nutrition, and Epidemiology, Harvard School of Public Health; Department of Medicine; Thoracic Surgery Unit, Department of Surgery, Massachusetts General Hospital; Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute; Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Pediatric Nutritional Sciences, Darby Children's Research Institute, Medical University of South Carolina, Charleston, SC

Address reprint requests to Wei Zhou, MD, PhD, Occupational Health Program, Harvard School of Public Health, 665 Huntington Ave, Boston, MA 02115; e-mail: wzhou{at}hsph.harvard.edu

Purpose Our previous analyses suggested that surgery in the summertime with higher vitamin D intake is associated with improved survival in patients with early-stage non–small-cell lung cancer (NSCLC). We further investigated the results of circulating 25-hydroxyvitamin D (25[OH]D) levels on overall survival (OS) and recurrence-free survival (RFS) in NSCLC patients.

Patients and Methods Among 447 patients with early-stage NSCLC, data were analyzed using Cox proportional hazards models, adjusting for age, sex, stage, smoking, and treatment.

Results The median follow-up time was 72 months (range, 0.2 to 141), with 161 recurrences and 234 deaths. For OS, the adjusted hazard ratio (AHR) was 0.74 (95% CI, 0.50 to 1.10; P_trend = .07) for the highest versus lowest quartile of 25(OH)D levels. Stratified by stage, a strong association was observed among stage IB-IIB patients (AHR, 0.45; 95% CI, 0.24 to 0.82; P_trend = .002), but not among stage IA patients (AHR, 1.10; 95% CI, 0.62 to 1.96; P_trend = .53). Similar effects of 25(OH)D levels were observed among the 309 patients with dietary information (AHR, 0.74; 95% CI, 0.46 to 1.17; P_trend = .19). For the joint effects of 25(OH)D level and vitamin D intake, the combined high 25(OH)D levels and high vitamin D intake (by median) were associated with better survival than the combined low 25(OH)D levels and low vitamin D intake (AHR, 0.64; 95% CI, 0.42 to 0.98; P_trend = .06). Again, stronger associations were observed among stage IB-IIB than IA patients. Similar effects of 25(OH)D levels and vitamin D intake were observed for RFS.

Conclusion Vitamin D may be associated with improved survival of patients with early-stage NSCLC, particularly among stage IB-IIB patients.

Supported by National Institutes of Health Grants No. CA 092824, CA074386, CA090578, ES/CA 06409, and ES00002 (D.C.C.); the American Institute for Cancer Research, the Flight Attendants Medical Research Institute Young Clinical Scientist Award, and NIH Grant No. CA119650-01A1 (W.Z.); the American Cancer Society Postdoctoral Fellowship (R.S.H.); and the Doris Duke Charitable Foundation and Sue's Fund (G.L.).

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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